Hazard Assessment and Contaminated Sites - Dealing with Contaminated Sites: From Theory Towards Practical Application - page 522

and identifying potential target organs or systems. It is important to note that, over
time, the scientific community will gain a better understanding of the mechanisms
of toxicity and this may lead to changes in both methodology and interpretation
of hazard data. Analysis and evaluation of toxicity studies should reflect scientific
consensus at the time the data are reviewed.
12.3.1 Toxicity Testing - Major In Vivo Study Types
Hazard Identification mostly relies on the results of in vivo toxicity studies con-
ducted according to standard protocols, e.g., OECD Test Guidelines (OECD 1998 ).
The following types of studies are defined:
Acute toxicity studies are studies which investigate the effects of single doses of
a contaminant. The LD 50 test, or medium lethal dose test which records gross
toxicity and mortality data over a 14 day post-dosing period, has been com-
monly employed, but newer tests (“limit” tests and “up-and-down” dosing
methods) are now favoured as they reduce the numbers of animals required
and reduce the suffering seen in the classical LD 50 test.
The standard acute toxicity studies include tests for acute oral, dermal and
inhalational toxicity, eye irritation, skin irritation and skin sensitisation. Such
studies may serve as the basis for classification and labelling of a particular
contaminant or contaminant mixture, and serve as an initial guide to possible
toxic modes of action and in establishing a dosing regimen in sub-chronic
toxicity studies.
Short term repeat-dose toxicity studies. A short-term study has been defined
(WHO 1990 ) as “having a duration lasting up to 10% of the animal's lifespan,
90 days in rats and mice, or 1 year in dogs”, although the US EPA considers
a 1-year dog study to be a chronic study. The main purpose of short term
repeat-dose testing is to identify any target organs and to establish dose levels
for chronic exposure studies.
Chronic toxicity studies , or long-term studies, are defined as studies lasting for
the greater part of the lifespan of the test animals, usually 18 months in mice,
two years in rats (WHO 1987 ; 1990 ). The protocol for these studies may
cover the investigation of chronic toxicity or carcinogenicity, or both.
Reproductive toxicity studies are studies designed to provide general informa-
tion about the effects of a test contaminant on reproductive performance in
both male and female animals, such as effects on mating behaviour, gonadal
function, oestrous cycling, conception, implantation, parturition, lactation,
weaning and neonatal mortality. These studies may also provide some infor-
mation about developmental or teratogenic effects of the test contaminant.
The conduct of and the results from these studies are very important to
assess with care, since the reproductive process is critical for perpetuation
of the species and factors or contaminant that alter or disrupt this process can
have devastating consequences, both in fact and in public perception (Korach
1998 ).